Abstract: The Translational Shared Research Core will provide services for both research projects in the CSB Center of HoPE. This program investigates tumor evolution as a dynamic process arising from selection (chemotherapy response, nutrient availability, oxygenation, therapy etc.) and phenotypic diversity resulting from genomic instability. This core is central to the mission of the proposal as it will collect, process, grow and maintain the patient-derived tumor cells in an effort to directly interrogate the subclonal populations found in patient tumor cells using both genomic and experimental approaches. Specifically, these cells will provide the basis for whole genome DNA sequencing to identify subclone populations present over the course of a patient's treatment or in multiple metastatic lesions in the projects. RNA sequencing of these patient cells will provide analysis of phenotypic evolution of patient cells in time or space, including the cell growth and survival pathways outlined in the projects. Lastly, these patient cells will be used in both projects to test the relationships between genomic and biochemical/pharmacological studies, including the ability to target key resistant cell phenotypes with drug regimens aimed at each patient's tumor cells. Importantly, this core is responsible for the generation of the sequencing data that provide the basis for the scientific projects above as well as sequencing the bulk tumor for comparison with the single cell sequencing and continue optimization of the single cell sequencing technology that is also central to the success of the scientific projects. The core will be responsible for generation of most genomic data, and disbursement of all sequencing data to identify genomic variants, evaluate subclonal structure, classify cellular phenotypes. These data will be made open to the scientific community following our first publication.